Journal article

Publication year: 2014

Pages: 7657-7660

Journal: Angewandte Chemie International Edition

Volume number: 53

Issue number: 29

ISSN: 1433-7851

eISSN: 1521-3773

DOI Link: https://doi.org/10.1002/anie.201403666

Publisher: Wiley

Abstract: 
Photochromic ligands have been used to control a variety of biological functions, especially in neural systems. Recently, much effort has been invested in the photocontrol of ion channels and G-protein coupled receptors found in the synapse. Herein, we describe the expansion of our photopharmacological approach toward the remote control of an enzyme. Building on hallmark studies dating from the late 1960s, we evaluated photochromic inhibitors of one of the most important enzymes in synaptic transmission, acetylcholinesterase (AChE). Using structure-based design, we synthesized several azobenzene analogues of the well-known AChE inhibitor tacrine (THA) and determined their effects on enzymatic activity. One of our compounds, AzoTHA, is a reversible photochromic blocker of AChE in vitro and ex vivo with high affinity and fast kinetics. As such, AzoTHA can be used to control synaptic transmission on the neuromuscular endplate based on the light-dependent clearance of a neurotransmitter.

Harvard Citation style: Broichhagen, J., Jurastow, I., Iwan, K., Kummer, W. and Trauner, D. (2014) Optical Control of Acetylcholinesterase with a Tacrine Switch, Angewandte Chemie International Edition, 53(29), pp. 7657-7660. https://doi.org/10.1002/anie.201403666

APA Citation style: Broichhagen, J., Jurastow, I., Iwan, K., Kummer, W., & Trauner, D. (2014). Optical Control of Acetylcholinesterase with a Tacrine Switch. Angewandte Chemie International Edition. 53(29), 7657-7660. https://doi.org/10.1002/anie.201403666